Major diabetes susceptibility gene discovered

A gene has been discovered that could make people with defective copies three times more likely to develop type 2 diabetes.

September 27, 2000

A gene has been discovered that could make people with defective copies three times more likely to develop type 2 diabetes. The discovery is published in October's issue of Nature Genetics. Scientists at the Howard Hughes Medical Institute at the University of Chicago and at the University of Texas, found that small genetic variations, called single-nucleotide polymorphisms (SNPs), in the gene for calpain-10 (a protease) are associated with type 2 diabetes. The association was demonstrated in Mexican Americans, who are susceptible to the disease. Sequencing DNA samples from this population and performing statistical analysis on the sequences, Dr Graeme Bell and his team found that these Mexican Americans had insulin resistance and showed reduced levels of calpain-10 gene expression, demonstrating that the polymorphism relates to the disease. The susceptibility-causing abnormality in the calpain-10 gene, surprisingly, occurs in an intron — non-functional genetic matter spliced out when DNA is transcribed into RNA. Dr Bell explained how difficult it was to find the gene because "diabetes is not a single disease but a group of related disorders with similar symptoms." He emphasised that the genetic variation does not cause diabetes by itself, but interacts with lifestyle factors such as diet, exercise and other genes. "We think it accounts for about 14% of the 'population attributable risk' in Mexican Americans and about 4% in Europeans." He hopes that the finding will encourage research into other genetically complex disorders such as asthma, schizophrenia and Alzheimer's disease.